Evidence map›Paper›PMID 41513585›Full record

ArticleAnnals of clinical and translational neurology2026

Characterization of Clinical Phenotype to Glial Fibrillary Acidic Protein Concentrations in Alexander Disease.

Amy T Waldman, Asako Takanohashi, Joshua Y Joung, Geraldine W Liu, Kaley Arnold, Amy Pizzino, Walter Faig, Sarah Woidill, Sona Narula, Adeline L Vanderver

Abstract read
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Article in Annals of clinical and translational neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Amy T WaldmanDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Asako TakanohashiDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Joshua Y JoungDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.ORCID 0009-0000-4151-4655
Geraldine W LiuDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Kaley ArnoldDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Amy PizzinoDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Walter FaigBiostatistics and Data Management Core, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Sarah WoidillDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Sona NarulaDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Adeline L VanderverDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-6290-6751

Funding

Validation of the GMFC-MLDU54NS115052 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI Laura Ann Adang, FLORIAN S EICHLER · 2019 to 2026
$14.3M
Elise's CornerGrayson's LadderIonis PharmaceuticalsNIH HHS U54NS115052
6 · The paper itself

Abstract

objectiveTo determine the concentration of glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF) and plasma in Alexander disease (AxD) and whether GFAP levels are predictive of disease phenotypes.

methodsCSF and plasma were collected (longitudinally when available) from AxD participants and non-AxD controls. The concentration of GFAP was compared between groups using Wilcoxon rank sum test. The Kruskal-Wallis test was used to compare GFAP concentrations across multiple groups (clinical phenotype or common genetic variants occurring at p.Arg79, p.Arg88, p.Arg239).

resultsGFAP concentrations were significantly elevated at baseline in both AxD CSF (N = 44) compared to controls (N = 46, p < 0.0001) and AxD plasma (N = 96) compared to other leukodystrophy plasma controls (N = 67, p < 0.0001). CSF and plasma GFAP concentrations differed between AxD cerebral, intermediate, and bulbospinal phenotypes (Kruskal-Wallis test, CSF: p = 0.0235, plasma: p < 0.0001). The median GFAP change/year among patients sampled < 8 years of age at baseline was an increase of 91,100 [pg/mL]/year (IQR 136,050) in CSF and 2850 [pg/mL]/year (IQR 9500) in plasma compared to patients > 8 years whose medians decreased over time (-41,000 [pg/mL]/year [IQR 90,300], CSF; -843 [pg/mL]/year [IQR 3900], plasma). The fold change in GFAP from first to last sampling were significantly different before and after 8 years at baseline (Wilcoxon rank sum test, CSF: p = 0.0232, plasma: p = 0.0002). A significant association was not detected between GFAP variant and GFAP levels.

interpretationGFAP concentrations are higher in the cerebral phenotype and increase over time in young children. These data can be used to formulate biomarker qualification and context-of-use in AxD.

Indexed as

Alexander DiseaseGlial Fibrillary Acidic ProteinAdolescentAdultBiomarkersChildChild, PreschoolFemaleHumansLongitudinal StudiesMalePhenotypeYoung AdultBiomarkersGFAP protein, humanGlial Fibrillary Acidic ProteinAlexander diseasebiomarkerGFAPleukodystrophy

Identifiers

PMID41513585
PMCPMC13251449

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.